tbuckley/cabot-search huggingface dataset:
Geographic Variation in Late-Stage Cervical Cancer Diagnosis
Authors: Itunu O. Sokale, Aaron P. Thrift, Jane Montealegre, Victor Adekanmbi, Onyema G. Chido-Amajuoyi, Ann Amuta, Lorraine R. Reitzel, Abiodun O. Oluyomi
Journal: JAMA Network Open (2023)

Importance There are stark disparities in cervical cancer burden in the United States, notably by race and ethnicity and geography. Late-stage diagnosis is an indicator of inadequate access to and utilization of screening. Objective To identify geospatial clusters of late-stage cervical cancer at time of diagnosis in Texas. Design, Setting, and Participants This population-based cross-sectional study used incident cervical cancer data from the Texas Cancer Registry from 2014 to 2018 of female patients aged 18 years or older. Late-stage cervical cancer cases were geocoded at the census tract level (n = 5265) using their residential coordinates (latitude and longitude) at the time of diagnosis. Statistical analysis was performed from April to September 2023. Exposures Census tract of residence at diagnosis. Main Outcome and Measures Late-stage cervical cancer diagnosis (ie, cases classified by the National Cancer Institute Surveillance, Epidemiology and End Results summary stages 2 to 4 [regional spread] or 7 [distant metastasis]). A Poisson probability-based model of the SaTScan purely spatial scan statistics was applied at the census tract–level to identify geographic clusters of higher (hot spots) or lower (cold spots) proportions than expected of late-stage cervical cancer diagnosis and adjusted for age. Results Among a total of 6484 female patients with incident cervical cancer cases (mean [SD] age, 48.7 [14.7] years), 2300 (35.5%) were Hispanic, 798 (12.3%) were non-Hispanic Black, 3090 (47.6%) were non-Hispanic White, and 296 (4.6%) were other race or ethnicity. Of the 6484 patients, 2892 with late-stage diagnosis (mean [SD] age, 51.8 [14.4] years were analyzed. Among patients with late-stage diagnosis, 1069 (37.0%) were Hispanic, 417 (14.4%) were non-Hispanic Black, 1307 (45.2%) were non-Hispanic White, and 99 (3.4%) were other race or ethnicity. SaTScan spatial analysis identified 7 statistically significant clusters of late-stage cervical cancer diagnosis in Texas, of which 4 were hot spots and 3 were cold spots. Hot spots included 1128 census tracts, predominantly in the South Texas Plains, Gulf Coast, and Prairies and Lakes (North Texas) regions. Of the 2892 patients with late-stage cervical cancer, 880 (30.4%) were observed within hot spots. Census tract–level comparison of characteristics of clusters suggested that hot spots differed significantly from cold spots and the rest of Texas by proportions of racial and ethnic groups, non–US born persons, and socioeconomic status. Conclusions and Relevance In this cross-sectional study examining geospatial clusters of late-stage cervical cancer diagnosis, place-based disparities were found in late-stage cervical cancer diagnosis in Texas. These findings suggest that these communities may benefit from aggressive cervical cancer interventions.
We Have More Tools to Support At-Risk Families Than Just Child Protective Services With Mandated Reporting
Authors: Bridget Freisthler
Journal: JAMA Pediatrics (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Health Disinformation Use Case Highlighting the Urgent Need for Artificial Intelligence Vigilance
Authors: Bradley D. Menz, Natansh D. Modi, Michael J. Sorich, Ashley M. Hopkins
Journal: JAMA Internal Medicine (2023)

Although artificial intelligence (AI) offers many promises across modern medicine, it may carry a significant risk for the mass generation of targeted health disinformation. This poses an urgent threat toward public health initiatives and calls for rapid attention by health care professionals, AI developers, and regulators to ensure public safety.
Alterations in intestinal Archaea composition in pediatric patients with Crohn’s disease based on next-generation sequencing – a pilot study
Authors: A. Krawczyk, T. Gosiewski, B. Zapała, K. Kowalska-Duplaga, D. Salamon
Journal: Gut Microbes (2023)

Intestinal dysbiosis can lead to the induction of systemic immune-mediated inflammatory diseases, such as Crohn's disease Although archaea are part of the commensal microbiota, they are still one of the least studied microorganisms. The aim of our study was the standardization of the optimal conditions and primers for sequencing of the gut archaeome using Next Generation Sequencing, and evaluation of the differences between the composition of archaea in patients and healthy volunteers, as well as analysis of the changes that occur in the archaeome of patients depending on disease activity. Newly diagnosed patients were characterized by similar archeal profiles at every taxonomic level as in healthy individuals (the dominance of Methanobacteria at the class level, and Methanobrevibacter at the genus level). In turn, in patients previously diagnosed with Crohn's disease (both in active and remission phase), an increased prevalence of Thermoplasmata, Thermoprotei, Halobacteria (at the class level), and Halococcus, Methanospaera or Picrophilus (at the genus level) were observed. Furthermore, we have found a significant correlation between the patient's parameters and the individual class or species of Archaea. Our study confirms changes in archaeal composition in pediatric patients with Crohn's disease, however, only in long-standing disease. At the beginning of the disease, the archeal profile is similar to that of healthy people. However, in the chronic form of the disease, significant differences in the composition of archaeome begin to appear. It seems that some archaea may be a good indicator of the chronicity and activity of Crohn's disease.
Single-cell atlas of healthy human blood unveils age-related loss of NKG2C+GZMB−CD8+ memory T cells and accumulation of type 2 memory T cells
Authors: Marina Terekhova, Amanda Swain, Pavla Bohacova, Ekaterina Aladyeva, Laura Arthur, Anwesha Laha, Denis A. Mogilenko, Samantha Burdess, Vladimir Sukhov, Denis Kleverov, Barbora Echalar, Petr Tsurinov, Roman Chernyatchik, Kamila Husarcikova, Maxim N. Artyomov
Journal: Immunity (2023)

Extensive, large-scale single-cell profiling of healthy human blood at different ages is one of the critical pending tasks required to establish a framework for the systematic understanding of human aging. Here, using single-cell RNA/T cell receptor (TCR)/BCR-seq with protein feature barcoding, we profiled 317 samples from 166 healthy individuals aged 25-85 years old. From this, we generated a dataset from ∼2 million cells that described 55 subpopulations of blood immune cells. Twelve subpopulations changed with age, including the accumulation of GZMK
Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial
Authors: Xiaomin Ou, Ruiping Zhai, Wenjun Wei, Jiaying Chen, Dan Ou, Tian Liao, Tingting Xu, Yongxue Zhu, Yulong Wang, Shenglin Huang, Rongliang Shi, Bin Wu, Tongzhen Chen, Yuan Li, Zhongyi Yang, Changming Zhou, Yuan Liu, Ziting Jiang, Min Zeng, Xin Liu, Dongmei Ji, Hongmei Ying, Zhen Zhang, Chaosu Hu, Xueguan Lu, Qinghai Ji, Xiayun He, Yu Wang
Journal: Clinical Cancer Research (2023)

The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer.
Sudden Cardiac Death in National Collegiate Athletic Association Athletes: A 20-Year Study
Authors: Bradley J. Petek, Timothy W. Churchill, Nathaniel Moulson, Stephanie A. Kliethermes, Aaron L. Baggish, Jonathan A. Drezner, Manesh R. Patel, Michael J. Ackerman, Kristen L. Kucera, David M. Siebert, Lauren Salerno, Monica Zigman Suchsland, Irfan M. Asif, Joseph J. Maleszewski, Kimberly G. Harmon
Journal: Circulation (2023)

BACKGROUND: Understanding the incidence, causes, and trends of sudden cardiac death (SCD) among young competitive athletes is critical to inform preventive policies. METHODS: This study included National Collegiate Athletic Association athlete deaths during a 20-year time frame (July 1, 2002, through June 30, 2022). Athlete deaths were identified through 4 separate independent databases and search strategies (National Collegiate Athletic Association resolutions list, Parent Heart Watch database and media reports, National Center for Catastrophic Sports Injury Research database, and insurance claims). Autopsy reports and medical history were reviewed by an expert panel to adjudicate causes of SCD. RESULTS: A total of 143 SCD cases in National Collegiate Athletic Association athletes were identified from 1102 total deaths. The National Collegiate Athletic Association resolutions list identified 117 of 143 (82%), the Parent Heart Watch database or media reports identified 89 of 143 (62%), the National Center for Catastrophic Sports Injury Research database identified 63 of 143 (44%), and insurance claims identified 27 of 143 (19%) SCD cases. The overall incidence of SCD was 1:63 682 athlete-years (95% CI, 1:54 065–1:75 010). Incidence was higher in male athletes than in female athletes (1:43 348 [95% CI, 1:36 228–1:51 867] versus 1:164 504 [95% CI, 1:110 552–1:244 787] athlete-years, respectively) and Black athletes compared with White athletes (1:26 704 [1:20 417–1:34 925] versus 1:74 581 [1:60 247–1:92 326] athlete-years, respectively). The highest incidence of SCD was among Division I male basketball players (1:8188 [White, 1:5848; Black, 1:7696 athlete-years]). The incidence rate for SCD decreased over the study period (5-year incidence rate ratio, 0.71 [95% CI, 0.61–0.82]), whereas the rate of noncardiovascular deaths remained stable (5-year incidence rate ratio, 0.98 [95% CI, 0.94–1.04]). Autopsy-negative sudden unexplained death (19.5%) was the most common postmortem examination finding, followed by idiopathic left ventricular hypertrophy or possible cardiomyopathy (16.9%) and hypertrophic cardiomyopathy (12.7%), in cases with enough information for adjudication (118 of 143). Eight cases of death were attributable to myocarditis over the study period (1 case from January 1, 2020, through June 30, 2022), with none attributed to COVID-19 infection. SCD events were exertional in 50% of cases. Exertional SCD was more common among those with coronary artery anomalies (100%) and arrhythmogenic cardiomyopathy (83%). CONCLUSIONS: The incidence of SCD in college athletes has decreased. Male sex, Black race, and basketball are associated with a higher incidence of SCD.
Facts and Hopes in Neoadjuvant Immunotherapy: Current Approvals and Emerging Evidence
Authors: Poorva Vaidya, Ezra E.W. Cohen
Journal: Clinical Cancer Research (2023)

Abstract In 2021 and 2022, two immune checkpoint inhibitors received FDA approval in the neoadjuvant setting for the treatment of early-stage triple negative breast cancer (TNBC) and non–small cell lung cancer (NSCLC). Several more studies have since indicated the benefits, and challenges, of administering neoadjuvant immunotherapy prior to definitive surgery in the gastrointestinal, head and neck, and cutaneous realms. In addition, numerous ongoing phase II and phase III trials are investigating outcomes of neoadjuvant immune treatment in early-stage disease. As such, it is anticipated that more immune checkpoint inhibitors will receive approval for various neoadjuvant indications in the next several years. Medical oncologists, surgeons, and other providers in a multidisciplinary cancer care team will be presented with alternate treatment paradigms and clinical decisions regarding upfront surgery versus neoadjuvant treatment. Here, we describe the current evidence supporting use of immune checkpoint inhibitors for neoadjuvant treatment, ongoing studies, and clinical considerations of this treatment approach.
Absence of <i>BTK</i>, <i>BCL2</i>, and <i>PLCG2</i> Mutations in Chronic Lymphocytic Leukemia Relapsing after First-Line Treatment with Fixed-Duration Ibrutinib plus Venetoclax
Authors: Nitin Jain, Lisa J. Croner, John N. Allan, Tanya Siddiqi, Alessandra Tedeschi, Xavier C. Badoux, Karl Eckert, Leo W.K. Cheung, Anwesha Mukherjee, James P. Dean, Edith Szafer-Glusman, John F. Seymour
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Mutations in BTK, PLCG2, and BCL2 have been reported in patients with progressive disease (PD) on continuous single-agent BTK or BCL2 inhibitor treatment. We tested for these mutations in samples from patients with PD after completion of first-line treatment with fixed-duration ibrutinib plus venetoclax for chronic lymphocytic leukemia (CLL) in the phase II CAPTIVATE study. Patients and Methods: A total of 191 patients completed fixed-duration ibrutinib plus venetoclax (three cycles of ibrutinib then 12–13 cycles of ibrutinib plus venetoclax). Genomic risk features [del(11q), del(13q), del(17p), trisomy 12, complex karyotype, unmutated IGHV, TP53 mutated] and mutations in genes recurrently mutated in CLL (ATM, BIRC3, BRAF, CHD2, EZH2, FBXW7, MYD88, NOTCH1, POT1, RPS15, SF3B1, XPO1) were assessed at baseline in patients with and without PD at data cutoff; gene variants and resistance-associated mutations in BTK, PLCG2, or BCL2 were evaluated at PD. Results: Of 191 patients completing fixed-duration ibrutinib plus venetoclax, with median follow-up of 38.9 months, 29 (15%) developed PD. No baseline risk feature or gene mutation was significantly associated with development of PD. No previously reported resistance-associated mutations in BTK, PLCG2, or BCL2 were detected at PD in 25 patients with available samples. Of the 29 patients with PD, 19 have required retreatment (single-agent ibrutinib, n = 16, or ibrutinib plus venetoclax, n = 3); 17 achieved partial response or better, 1 achieved stable disease, and 1 is pending response assessment. Conclusions: First-line fixed-duration combination treatment with ibrutinib plus venetoclax may mitigate development of resistance mechanisms associated with continuous single-agent targeted therapies, allowing for effective retreatment. See related commentary by Al-Sawaf and Davids, p. 471
Growth factor free, peptide-functionalized gelatin hydrogel promotes arteriogenesis and attenuates tissue damage in a murine model of critical limb ischemia
Authors: Corinne W Curry, Sarah M Sturgeon, Brian J O'Grady, Alexis Yates, Andrew Kjar, Hayden Paige, Lucas S Mowery, Ketaki A Katdare, Riya Patel, Kate Mlouk, Madison R Stiefbold, Sidney Vafaie-Partin, Atsuyuki Kawabata, Rachel McKee, Stephanie Moore-Lotridge, Adrienne Hawkes, Jiro Kusunose, Katherine N Gibson-Corley, Jeffrey Schmeckpeper, Jonathan G Schoenecker, Charles F Caskey, Ethan S Lippmann
Journal: Biomaterials (2023)
Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation
Authors: Hannah Knight, Giancarlo Abis, Manpreet Kaur, Hannah L.H. Green, Susanne Krasemann, Kristin Hartmann, Steven Lynham, James Clark, Lan Zhao, Clemens Ruppert, Astrid Weiss, Ralph T. Schermuly, Philip Eaton, Olena Rudyk
Journal: Circulation Research (2023)

Pulmonary hypertension (PH) is a chronic vascular disease characterized, among other abnormalities, by hyperproliferative smooth muscle cells and a perturbed cellular redox and metabolic balance. Oxidants induce cell cycle arrest to halt proliferation; however, little is known about the redox-regulated effector proteins that mediate these processes. Here, we report a novel kinase-inhibitory disulfide bond in cyclin D-CDK4 (cyclin-dependent kinase 4) and investigate its role in cell proliferation and PH.
DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters
Authors: Nienke M. Stege, Tim R. Eijgenraam, Vivian Oliveira Nunes Teixeira, Anna M. Feringa, Elisabeth M. Schouten, Diederik W.D. Kuster, Jolanda van der Velden, Anouk H.G. Wolters, Ben N.G. Giepmans, Catherine A. Makarewich, Rhonda Bassel-Duby, Eric N. Olson, Rudolf A. de Boer, Herman H.W. Silljé
Journal: Circulation Research (2023)

BACKGROUND: The p.Arg14del variant of the PLN (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease. Dwarf open reading frame (DWORF) has been shown to counteract PLN regulatory calcium handling function in the sarco/endoplasmic reticulum (S/ER). Here, we investigated the potential disease-modulating action of DWORF in this cardiomyopathy and its effects on calcium handling and PLN aggregation. METHODS: We studied a PLN-R14del mouse model, which develops cardiomyopathy with similar characteristics as human patients, and explored whether cardiac DWORF overexpression could delay cardiac deterioration. To this end, R14 Δ/Δ (homozygous PLN-R14del) mice carrying the DWORF transgene (R14 Δ/Δ DWORF Tg [R14 Δ/Δ mice carrying the DWORF transgene]) were used. RESULTS: DWORF expression was suppressed in hearts of R14 Δ/Δ mice with severe heart failure. Restoration of DWORF expression in R14 Δ/Δ mice delayed cardiac fibrosis and heart failure and increased life span &gt;2-fold (from 8 to 18 weeks). DWORF accelerated sarcoplasmic reticulum calcium reuptake and relaxation in isolated cardiomyocytes with wild-type PLN, but in R14 Δ/Δ cardiomyocytes, sarcoplasmic reticulum calcium reuptake and relaxation were already enhanced, and no differences were detected between R14 Δ/Δ and R14 Δ/Δ DWORF Tg . Rather, DWORF overexpression delayed the appearance and formation of large pathogenic perinuclear PLN clusters. Careful examination revealed colocalization of sarcoplasmic reticulum markers with these PLN clusters in both R14 Δ/Δ mice and human p.Arg14del PLN heart tissue, and hence these previously termed aggregates are comprised of abnormal organized S/ER. This abnormal S/ER organization in PLN-R14del cardiomyopathy contributes to cardiomyocyte cell loss and replacement fibrosis, consequently resulting in cardiac dysfunction. CONCLUSIONS: Disorganized S/ER is a major characteristic of PLN-R14del cardiomyopathy in humans and mice and results in cardiomyocyte death. DWORF overexpression delayed PLN-R14del cardiomyopathy progression and extended life span in R14 Δ/Δ mice, by reducing abnormal S/ER clusters.
NAT10 Is Involved in Cardiac Remodeling Through ac4C-Mediated Transcriptomic Regulation
Authors: Jing Shi, Chuanxi Yang, Jing Zhang, Kun Zhao, Peng Li, Chuiyu Kong, Xiaoguang Wu, Haoliang Sun, Rui Zheng, Wei Sun, Lianmin Chen, Xiangqing Kong
Journal: Circulation Research (2023)

BACKGROUND: Heart failure, characterized by cardiac remodeling, is associated with abnormal epigenetic processes and aberrant gene expression. Here, we aimed to elucidate the effects and mechanisms of NAT10 (N-acetyltransferase 10)-mediated N4-acetylcytidine (ac4C) acetylation during cardiac remodeling. METHODS: NAT10 and ac4C expression were detected in both human and mouse subjects with cardiac remodeling through multiple assays. Subsequently, acetylated RNA immunoprecipitation and sequencing, thiol-linked alkylation for the metabolic sequencing of RNA (SLAM-seq), and ribosome sequencing (Ribo-seq) were employed to elucidate the role of ac4C-modified posttranscriptional regulation in cardiac remodeling. Additionally, functional experiments involving the overexpression or knockdown of NAT10 were conducted in mice models challenged with Ang II (angiotensin II) and transverse aortic constriction. RESULTS: NAT10 expression and RNA ac4C levels were increased in in vitro and in vivo cardiac remodeling models, as well as in patients with cardiac hypertrophy. Silencing and inhibiting NAT10 attenuated Ang II-induced cardiomyocyte hypertrophy and cardiofibroblast activation. Next-generation sequencing revealed ac4C changes in both mice and humans with cardiac hypertrophy were associated with changes in global mRNA abundance, stability, and translation efficiency. Mechanistically, NAT10 could enhance the stability and translation efficiency of CD47 and ROCK2 transcripts by upregulating their mRNA ac4C modification, thereby resulting in an increase in their protein expression during cardiac remodeling. Furthermore, the administration of Remodelin, a NAT10 inhibitor, has been shown to prevent cardiac functional impairments in mice subjected to transverse aortic constriction by suppressing cardiac fibrosis, hypertrophy, and inflammatory responses, while also regulating the expression levels of CD47 and ROCK2 (Rho associated coiled-coil containing protein kinase 2). CONCLUSIONS: Therefore, our data suggest that modulating epitranscriptomic processes, such as ac4C acetylation through NAT10, may be a promising therapeutic target against cardiac remodeling.
Hydrogel‐Embedded Precision‐Cut Lung Slices Model Lung Cancer Premalignancy Ex Vivo
Authors: Rachel Blomberg, Kayla Sompel, Caroline Hauer, Alex J. Smith, Brisa Peña, Jennifer Driscoll, Patrick S. Hume, Daniel T. Merrick, Meredith A. Tennis, Chelsea M. Magin
Journal: Advanced Healthcare Materials (2023)

Abstract Lung cancer is the leading global cause of cancer‐related deaths. Although smoking cessation is the best prevention, 50% of lung cancer diagnoses occur in people who have quit smoking. Research into treatment options for high‐risk patients is constrained to rodent models, which are time‐consuming, expensive, and require large cohorts. Embedding precision‐cut lung slices (PCLS) within an engineered hydrogel and exposing this tissue to vinyl carbamate, a carcinogen from cigarette smoke, creates an in vitro model of lung cancer premalignancy. Hydrogel formulations are selected to promote early lung cancer cellular phenotypes and extend PCLS viability to six weeks. Hydrogel‐embedded PCLS are exposed to vinyl carbamate, which induces adenocarcinoma in mice. Analysis of proliferation, gene expression, histology, tissue stiffness, and cellular content after six weeks reveals that vinyl carbamate induces premalignant lesions with a mixed adenoma/squamous phenotype. Putative chemoprevention agents diffuse through the hydrogel and induce tissue‐level changes. The design parameters selected using murine tissue are validated with hydrogel‐embedded human PCLS and results show increased proliferation and premalignant lesion gene expression patterns. This tissue‐engineered model of human lung cancer premalignancy is the foundation for more sophisticated ex vivo models that enable the study of carcinogenesis and chemoprevention strategies.
Risk-directed therapy based on genetics and MRD improves the outcomes of AML1-ETO-positive AML patients, a multi-center prospective cohort study
Authors: Dan Xu, Ying Yang, Zhao Yin, Sanfang Tu, Danian Nie, Yiqing Li, Zhenqian Huang, Qixin Sun, Changfen Huang, Xiaqi Nie, Zurong Yao, Pengcheng Shi, Yu Zhang, Xuejie Jiang, Qifa Liu, Guopan Yu
Journal: Blood Cancer Journal (2023)